A randomized embedded multifactorial adaptive platform for extra corporeal membrane oxygenation (REMAP ECMO) – design and rationale of the left ventricular unloading trial domain - 02/12/24

Doi : 10.1016/j.ahj.2024.10.010

Myrthe P.J. van Steenwijk, MD ^a,^b, Joost van Rosmalen, PhD ^c,^d, Carlos V. Elzo Kraemer, MD ^e, Dirk W. Donker, MD, PhD ^f,^g, Jeannine A.J.M. Hermens, MD ^f, Adriaan O. Kraaijeveld, MD, PhD ^h, Jacinta J. Maas, MD, PhD ^e, Sakir Akin, MD, PhD ⁱ, Leon J. Montenij, MD, PhD ^j, Alexander P.J. Vlaar, MD, PhD ^k, Walter M. van den Bergh, MD, PhD ^l, Annemieke Oude Lansink-Hartgring, MD, PhD ^l, Jesse de Metz, MD ^m, Niek Voesten, MD ⁿ, Eric Boersma, PhD ^b, Erik Scholten, MD, PhD ^o, Albertus Beishuizen, MD, PhD ^p, Chris P.H. Lexis, MD, PhD ^q, Harlinde Peperstraete, MD, PhD ^r, Simon Schiettekatte, MD, PhD ^s, Roberto Lorusso, MD, PhD ^t, Diederik A.M.P.J. Gommers, MD, PhD ^a, Dick Tibboel, MD, PhD ^a, Rudolf A. de Boer, MD, PhD ^b, Nicolas M.D.A. Van Mieghem, MD, PhD ^b, Christiaan L. Meuwese, MD, PhD ^a,^b,^⁎
On behalf of the
REMAP ECMO LV unloading study group
^a Department of Intensive Care, Erasmus Medical Center, Rotterdam, the Netherlands
^b Department of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus Medical Center, Rotterdam, the Netherlands
^c Departments of Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands
^d Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
^e Department of Intensive Care, Leiden University Medical Center, Leiden, the Netherlands
^f Department of Intensive Care, University Medical Center Utrecht, Utrecht, the Netherlands
^g Cardiovascular and Respiratory Physiology, University of Twente, Enschede, the Netherlands
^h Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands
ⁱ Department of Intensive Care, Haga Hospital, The Hague, the Netherlands
^j Department of Intensive Care, Catharina Hospital Eindhoven, Eindhoven, the Netherlands
^k Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, the Netherlands
^l Department of Critical Care, University Medical Center Groningen, Groningen, the Netherlands
^m Department of Intensive Care, OLVG Amsterdam, Amsterdam, the Netherlands
ⁿ Department of Intensive Care, Amphia Hospital Breda, Breda, the Netherlands
^o Department of Intensive Care, Sint Antonius Hospital, Nieuwegein, the Netherlands
^p Department of Intensive Care, Medisch Spectrum Twente, Enschede, the Netherlands
^q Department of Intensive Care and Cardiology, Maastricht UMC, Maastricht, the Netherlands
^r Department of Intensive Care, Ghent University Hospital, Ghent, Belgium
^s Department of Cardiac Surgery, Ziekenhuis Oost-Limburg Genk, Genk, Belgium
^t Department of Cardiothoracic Surgery and Cardiovascular Research Center, Maastricht UMC, Maastricht, the Netherlands

^⁎Reprint requests: C.L. Meuwese, MD, PhD, Department of Intensive Care, Erasmus Medical Center, Dr. Molewaterplein 40, 3015GD Rotterdam, the NetherlandsDepartment of Intensive CareErasmus Medical Center Dr. Molewaterplein 40Rotterdam3015GDthe Netherlands

ABSTRACT

Background

The use of Extracorporeal Membrane Oxygenation (ECMO) remains associated with high rates of complications, weaning failure and mortality which can be partly explained by a knowledge gap on how to properly manage patients on ECMO support. To address relevant patient management issues, we designed a “Randomized Embedded Multifactorial Adaptive Platform (REMAP)” in the setting of ECMO (REMAP ECMO) and a first embedded randomized controlled trial (RCT) investigating the effects of routine early left ventricular (LV) unloading through intra-aortic balloon pumping (IABP).

Methods

REMAP ECMO describes a registry-based platform allowing for the embedding of multiple response adaptive RCTs (trial domains) which can perpetually address the effect of relevant patient management issues on ECMO weaning success. A first trial domain studies the effects of LV unloading by means of an IABP as an adjunct to veno-arterial (V-A) ECMO versus V-A ECMO alone on ECMO weaning success at 30 days in adult cardiogenic shock patients admitted to the Intensive Care Unit (ICU). The primary outcome of this trial is “successful weaning from ECMO” being defined as a composite of survival without the need for mechanical circulatory support, heart transplantation, or left ventricular assist device (LVAD) at 30 days after initiation of ECMO. Secondary outcomes include the need for interventional escalation of LV unloading strategy, mechanistic endpoints, survival characteristics until 1 year after ECMO initiation, and quality of life. Trial data will be analysed using a Bayesian statistical framework. The adaptive design allows for a high degree of flexibility, such as response adaptive randomization and early stopping of the trial for efficacy or futility. The REMAP ECMO LV unloading study is approved by the Medical Ethical Committee of the Erasmus Medical Center and is publicly registered.

Conclusion

This REMAP ECMO trial platform enables the efficient roll-out of multiple RCTs on relevant patient management issues. A first embedded trial domain will compare routine LV unloading by means of an IABP as an adjunct to V-A ECMO versus V-A ECMO alone.

Trial registration

ClinicalTrials.gov, NCT05913622

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Plan

Background

Rationale of the LV unloading trial domain

Methods

LV unloading trial design

Endpoints

Statistical analysis

Response adaptive randomization

Sample size calculation

Current status of the study

Safety monitoring

Data management

Ethics and dissemination

Discussion

Conclusion

CRediT authorship contribution statement

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Vol 279

P. 81-93 - janvier 2025 Retour au numéro

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A randomized embedded multifactorial adaptive platform for extra corporeal membrane oxygenation (REMAP ECMO) – design and rationale of the left ventricular unloading trial domain - 02/12/24

ABSTRACT

Background

Methods

Conclusion

Trial registration

Plan

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